Epoetin Alfa or Darbepoetin Alfa in Treating Patients With Anemia Caused by Chemotherapy - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00416624

Purpose

RATIONALE: Epoetin alfa and darbepoetin alfa may cause the body to make more red blood cells. They are used to treat anemia caused by chemotherapy in patients with cancer.

PURPOSE: This randomized clinical trial is studying four different schedules of epoetin alfa or darbepoetin alfa to compare how well they work in treating patients with anemia caused by chemotherapy.

Condition	Intervention
Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific	Drug: darbepoetin alfa Drug: epoetin alfa Procedure: fatigue assessment and management Procedure: quality-of-life assessment

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Supportive Care
Official Title:	RC05CB A Pilot, Randomized Comparison of Standard Weekly Epoetin Alfa to Every-3-Week-Epoetin Alfa and Every 3-Week Darbepoetin Alfa

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Acute Lymphocytic Leukemia Anemia Cancer Chronic Lymphocytic Leukemia Fatigue Fungal Infections Hodgkin Disease Leukemia Lymphoma Multiple Myeloma

Drug Information available for: Erythropoietin Epoetin alfa Darbepoetin alfa

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:

Hematopoietic response (hemoglobin rise of 2 g/dL from baseline OR achievement of hemoglobin within the goal range) [ Time Frame: 20 weeks ]
the proportion of patients who exhibit a hematopoietic response (defined as Hb rise >2 g/dL from baseline or achieving Hb ≥ 11.5 g/dL, whichever occurs first, in the absence of RBC transfusions within 14 days of measurement) during the treatment period

Secondary Outcome Measures:

Weekly change in hemoglobin levels [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa
Time required to achieve hemoglobin levels within the goal range [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa
Proportion of patients requiring red blood cell (RBC) transfusions and the number of transfusions required [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa
Dose reduction in each regimen [ Designated as safety issue: No ]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa
Adverse events as measured by CTCAE v3.0 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa
Quality of life as measured by Functional Assessment of Cancer Therapy Scales for Anemia, Linear Analogue Self Assessment measures, Brief Fatigue Inventory, and Symptom Distress Scale at baseline and at 4, 8, 16, and 24 weeks [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
To compare the effects of the 3 different epoetin alfa dosing schedules and a darbepoetin alfa
Mean hemoglobin increment week by week [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
To compare the effects of the 3 different epoetin alfa dosing schedules and an every-3-weeks darbepoetin alfa

Estimated Enrollment:	320
Study Start Date:	May 2007
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Epoetin alfa - 40000 units 40,000 Units	Drug: darbepoetin alfa Drug: epoetin alfa Procedure: fatigue assessment and management Procedure: quality-of-life assessment
Experimental: Epoetin alfa - 80000 units 80,000 Units	Drug: darbepoetin alfa Drug: epoetin alfa Procedure: fatigue assessment and management Procedure: quality-of-life assessment
Experimental: Epoetin alfa - 120000 Units 120,000 Units	Drug: darbepoetin alfa Drug: epoetin alfa Procedure: fatigue assessment and management Procedure: quality-of-life assessment
Experimental: Darbepoetin alfa*** 500 mcg	Drug: darbepoetin alfa Drug: epoetin alfa Procedure: fatigue assessment and management Procedure: quality-of-life assessment

Detailed Description:

OBJECTIVES:

Primary

Compare the relative efficacy of four different erythropoietic agent dosing schedules comprising epoetin alfa or darbepoetin alfa, in terms of the proportion of patients with chemotherapy-associated anemia who achieve a weekly and overall hematopoietic response.

Secondary

Compare the effect of these regimens on the mean hemoglobin increment measured weekly from baseline to 15 weeks in patients with a baseline hemoglobin of less than or equal to 10.5 g/dL.
Compare the time required to achieve hemoglobin levels within the goal range 11.0-12.0 g/dL in patients treated with these regimens.
Compare the effect of these regimens on the proportion of patients requiring red blood cell transfusions and on the number of transfusions required.
Compare the weekly change in hemoglobin in patients treated with these regimens.
Compare the need for dose reduction in patients treated with these regimens.
Compare the adverse event profiles of these regimens in these patients.
Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, unblinded, pilot study. Patients are stratified according to severity of anemia (mild [hemoglobin ≥ 9.5 g/dL] vs severe [hemoglobin < 9.5 g/dL]), platinum-containing regimen (yes vs no), and tumor type (nonmyeloid hematologic malignancy vs solid tumor). Patients are randomized to 1 of 4 treatment arms.

Arm I: Patients receive epoetin alfa subcutaneously (SC) on day 1. Treatment repeats weekly for up to 15 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm I). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
Arm III: Patients receive epoetin alfa SC on day 1 (at a higher dose than in arm II). Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.
Arm IV: Patients receive darbepoetin alfa SC on day 1. Treatment repeats every 3 weeks for up to 5 courses in the absence of disease progression or unacceptable toxicity.

Hemoglobin levels are monitored throughout the study on a weekly basis and before each drug dose is administered. Drug dosing is adjusted (e.g., held, reduced, resumed at a lower dose) as needed to maintain hemoglobin values within the desired ranges.

Quality of life is assessed at baseline and at weeks 4, 7, 10, 13, and 16.

After completion of study treatment, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 320 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of solid tumor or nonmyeloid hematologic malignancy (e.g., plasma cell dyscrasia or lymphoproliferative disorder)
- No nonmelanomatous skin cancer
Hemoglobin ≤ 10.5 g/dL
Ferritin > 20 ng/mL (i.e., not obviously iron deficient)
Planning to receive ≥ 12 weeks of anticancer chemotherapy
- Biological therapy (e.g., hypomethylating agents, monoclonal antibodies, or small molecule pathway inhibitors) with an individual or cumulative regimen incidence of grade 3 or 4 anemia > 10% is considered chemotherapy for purposes of this study
No known anemia secondary to any of the following:
- Cyanocobalamin (vitamin B_12) or folic acid deficiency
- Gastrointestinal bleeding within the past 2 weeks
- Hemolysis
- Myelodysplastic syndromes, myeloproliferative disorders, or acute myeloid leukemia
No primary hematologic disorder causing chronic moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major)
- Carriers of these disease states allowed provided they are not anemic prior to cancer diagnosis

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 6 months
Not pregnant or nursing
- No delivery of a baby of ≥ 18 weeks estimated gestational age within the past 3 months (90 days)
Negative pregnancy test
Fertile patients must use effective contraception
Weight > 40.0 kg and < 150.0 kg
No known hypersensitivity to epoetin alfa, darbepoetin alfa, mammalian-cell derived products, or human albumin
No uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 180 mm Hg and/or diastolic BP ≥ 100 mm Hg, despite medical therapy
No pulmonary emboli and/or deep vein thrombosis within the past 12 months
- Patients actively receiving warfarin for a minimum of 4 weeks are exempted from this requirement
- Prior superficial thrombophlebitis allowed
No cerebrovascular accident, ischemic stroke, acute coronary syndrome (e.g., unstable angina or Q-wave or non-Q wave myocardial infarction), or other arterial or venous thrombotic events within the past 6 months
No history of chronic hypercoagulable disorders (e.g., activated protein C resistance, anti-cardiolipin disorder, protein C deficiency, or protein S deficiency)
- Patients receiving anticoagulation therapy (warfarin or acetylsalicyclic acid [aspirin] at a dose of ≥ 325 mg/day) for these conditions are eligible provided therapy is continued during the study period
History of previously treated seizures allowed provided the patient has been seizure-free for a minimum of 3 months

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 1 year since prior peripheral blood stem cell, bone marrow, or cord blood transplantation
More than 14 days since prior red blood cell transfusion
More than 14 days since prior major surgery, including, but not limited to, any of the following:
- Amputation
- Invasion of a body cavity or of the central nervous system using a scalpel, saw, or laser cutting tool
- Resection of a body part (or parts), whether solid or liquid tissue or both, that includes ≥ 1% of a patient's preoperative weight
- The following are not considered major surgery:
  - Diagnostic/therapeutic thoracentesis or paracentesis
  - Diagnostic skin biopsy
  - Digit or fingernail/thumbnail resection or laceration repair under local anesthesia
  - Diagnostic fat aspiration
  - Otic irrigation to remove cerumen impaction
  - Tympanocentesis
  - Uncomplicated dental extraction
  - Uncomplicated tonsillectomy
  - Laser corneal remodeling for refraction purposes
  - Cosmetic or therapeutic eyelid surgery
  - Bone marrow aspiration and biopsy
More than 10 weeks since prior darbepoetin alfa, epoetin alfa, or any investigational form of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis stimulating protein)
No planned stem cell transplantation within the next 4 months (18 weeks)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00416624

Locations

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Charles L. Loprinzi, M.D.

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Charles Lawrence Loprinzi, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier:	NCT00416624 History of Changes
Other Study ID Numbers:	CDR0000522677, P30CA015083, RC05CB, 06-002991, EPOANE3015
Study First Received:	December 27, 2006
Last Updated:	March 16, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mayo Clinic:

unspecified adult solid tumor, protocol specific
extramedullary plasmacytoma
isolated plasmacytoma of bone
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
Waldenstrom macroglobulinemia
post-transplant lymphoproliferative disorder
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
AIDS-related peripheral/systemic lymphoma

AIDS-related primary CNS lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma

Additional relevant MeSH terms:

Anemia
Neoplasms
Disease
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Precancerous Conditions
Lymphoma, Large-Cell, Immunoblastic
Hematologic Diseases
Pathologic Processes
Neoplasms by Histologic Type

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Darbepoetin alfa
Epoetin Alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012